Risk Factors and Contemporary Management Options for Pain and Discomfort Experienced During a Prostate Biopsy.

PURPOSE OF REVIEW: Prostate fusion biopsy, an innovative imaging modality for diagnosing prostate cancer, presents certain challenges for patients including discomfort and emotional distress, leading to nonadherence to treatment and follow-ups. To inform clinicians and offer pain relief alternatives to patients, this review delves into the risk factors for increased pain and modern management options to alleviate pain during prostate biopsy. RECENT FINDINGS: Individual responses to pain vary, and the overall experience of pain during a prostate biopsy has been contributed to numerous factors such as patient age, prostate volume, previous biopsy experience, and more. As a result, several strategies aim to mitigate pain during in-office procedures. Notably, techniques including pharmacological analgesics, hand holding, heating pads, entertainment/virtual reality, and distraction have shown significant efficacy. Existing studies explore risk factors influencing pain intensity during prostate biopsy and effective pain management strategies. This review consolidates available information to guide clinicians in enhancing patient comfort and thus, encourage surveillance adherence.

The effect of a fermented soy beverage among patients with localized prostate cancer prior to radical prostatectomy.

BACKGROUND: Fermented soy products have shown to possess inhibitory effects on prostate cancer (PCa). We evaluated the effect of a fermented soy beverage (Q-Can®), containing medium-chain triglycerides, ketones and soy isoflavones, among men with localized PCa prior to radical prostatectomy. METHODS: We conducted a placebo-controlled, double-blind randomized trial of Q-Can®. Stratified randomization (Cancer of the Prostate Risk Assessment (CAPRA) score at diagnosis) was used to assign patients to receive Q-Can® or placebo for 2-5 weeks before RP. Primary endpoint was change in serum PSA from baseline to end-of-study. We assessed changes in other clinical and pathologic endpoints. The primary ITT analysis compared PSA at end-of-study between randomization arms using repeated measures linear mixed model incorporating baseline CAPRA risk strata. RESULTS: We randomized 19 patients, 16 were eligible for analysis of the primary outcome. Mean age at enrollment was 61, 9(56.2%) were classified as low and intermediate risk, and 7(43.8%) high CAPRA risk. Among patients who received Q-Can®, mean PSA at baseline and end-of-study was 8.98(standard deviation, SD 4.07) and 8.02ng/mL(SD 3.99) compared with 8.66(SD 2.71) to 9.53ng/mL(SD 3.03), respectively, (Difference baseline - end-of-study, p = 0.36). There were no significant differences in Gleason score, clinical stage, surgical margin status, or CAPRA score between treatment arms (p > 0.05), and no significant differences between treatment arms in end-of-study or change in lipids, testosterone and FACT-P scores (p > 0.05). CONCLUSIONS: Short exposure to Q-Can® among patients with localized PCa was not associated with changes in PSA levels, PCa characteristics including grade and stage or serum testosterone. Due to early termination from inability to recruit, study power, was not achieved.

Personalizing approaches to the management of metastatic hormone sensitive prostate cancer: role of advanced imaging, genetics and therapeutics.

PURPOSE: To summarize contemporary and emerging strategies for the diagnosis and management of metastatic hormone sensitive prostate cancer (mHSPC), focusing on diagnostic testing and therapeutics. METHODS: Literature review using PUBMED-Medline databases as well as clinicaltrials.gov to include reported or ongoing clinical trials on treatment for mHSPC. We prioritized the findings from phase III randomized clinical trials, systematic reviews, meta-analyses and clinical practice guidelines. RESULTS: There have been significant changes to the diagnosis and staging evaluation of mHSPC with the integration of increasingly accurate positron emission tomography (PET) imaging tracers that exceed the performance of conventional computerized tomography (CT) and bone scan. Germline multigene testing is recommended for the evaluation of patients newly diagnosed with mHSPC given the prevalence of actionable alterations that may create candidacy for specific therapies. Although androgen deprivation therapy (ADT) remains the backbone of treatment for mHSPC, approaches to first-line treatment include the integration of multiple agents including androgen receptor synthesis inhibitors (ARSI; abiraterone) Androgen Receptor antagonists (enzalutamide, darolutamide, apalautamide), and docetaxel chemotherapy. The combination of ADT, ARSI, and docetaxel chemotherapy has recently been evaluated in a randomized trial and was associated with significantly improved overall survival including in patients with a high burden of disease. The role of local treatment to the prostate with radiation has been evaluated in randomized trials with additional studies underway evaluating the role of cytoreductive radical prostatectomy. CONCLUSION: The staging and initial management of patients with mHSPC has undergone significant advances in the last decade with advancements in the diagnosis, treatment and sequencing of therapies.

Local Therapeutics for the Treatment of Oligo Metastatic Prostate Cancer.

PURPOSE OF REVIEW: Metastatic prostate cancer remains universally lethal. Although de-novo metastatic prostate cancer was historically managed with systemic therapy alone, local therapies are increasingly utilized in the early treatment of the disease, particularly in patients with oligometastatic prostate cancer (OMPC). OMPC represents an intermediate stage between clinically localized and widespread metastatic disease. Diseases classified within this stage present an opportunity for localized targeting of the disease prior to progression to widespread metastases. The purpose of this review is to discuss the contemporary and emerging local therapies for the treatment of OMPC. RECENT FINDINGS: To date, there are three utilized forms of local therapy for OMPC: cryoablation, radiation therapy, and cytoreductive prostatectomy. Cryoablation can be utilized for the total ablation of the prostate and has shown promising results in patients with OMPC either in combination with ADT or with ADT and systemic chemotherapy. Radiation therapy along with ADT has demonstrated improvement in progression-free survival. The STAMPEDE Arm G, PEACE-1, and the HORRAD clinical trials have investigated radiation therapy for mPCa compared to standard of care versus systemic therapy with varying results. Cytoreductive radical prostatectomy (CRP) in conjunction with ADT has also been proposed in the management of OPMC with promising results from case-control and retrospective studies. Currently there are larger controlled trials investigating CRP for OPMC including the SIMCAP, LoMP, TRoMbone, SWOG 1802, IP2-ATLANTA, g-RAMPP, and FUSCC-OMPCa trials. Given the novel nature of local treatments for OPMC, treatment selection is still controversial and requires long-term follow-up and randomized clinical trials to aid patient and clinician decision making.

Targeting hyaluronic acid synthase-3 (HAS3) for the treatment of advanced renal cell carcinoma.

BACKGROUND: Hyaluronic acid (HA) promotes cancer metastasis; however, the currently approved treatments do not target HA. Metastatic renal carcinoma (mRCC) is an incurable disease. Sorafenib (SF) is a modestly effective antiangiogenic drug for mRCC. Although only endothelial cells express known SF targets, SF is cytotoxic to RCC cells at concentrations higher than the pharmacological-dose (5-µM). Using patient cohorts, mRCC models, and SF combination with 4-methylumbelliferone (MU), we discovered an SF target in RCC cells and targeted it for treatment. METHODS: We analyzed HA-synthase (HAS1, HAS2, HAS3) expression in RCC cells and clinical (n = 129), TCGA-KIRC (n = 542), and TCGA-KIRP (n = 291) cohorts. We evaluated the efficacy of SF and SF plus MU combination in RCC cells, HAS3-transfectants, endothelial-RCC co-cultures, and xenografts. RESULTS: RCC cells showed increased HAS3 expression. In the clinical and TCGA-KIRC/TCGA-KIRP cohorts, higher HAS3 levels predicted metastasis and shorter survival. At > 10-µM dose, SF inhibited HAS3/HA-synthesis and RCC cell growth. However, at ≤ 5-µM dose SF in combination with MU inhibited HAS3/HA synthesis, growth of RCC cells and endothelial-RCC co-cultures, and induced apoptosis. The combination inhibited motility/invasion and an HA-signaling-related invasive-signature. We previously showed that MU inhibits SF inactivation in RCC cells. While HAS3-knockdown transfectants were sensitive to SF, ectopic-HAS3-expression induced resistance to the combination. In RCC models, the combination inhibited tumor growth and metastasis with little toxicity; however, ectopic-HAS3-expressing tumors were resistant. CONCLUSION: HAS3 is the first known target of SF in RCC cells. In combination with MU (human equivalent-dose, 0.6-1.1-g/day), SF targets HAS3 and effectively abrogates mRCC.

Optimal Use of Tumor-Based Molecular Assays for Localized Prostate Cancer.

PURPOSEOF REVIEW: The use of genomic testing for prostate cancer continues to grow; however, utilization remains institutionally dependent. Herein, we review current tissue-based markers and comment on current use with active surveillance and prostate MRI. RECENT FINDINGS: While data continues to emerge, several studies have shown a role for genomic testing for treatment selection. Novel testing options include ConfirmMDx, ProMark, Prolaris, and Decipher, which have shown utility in select patients. The current body of literature on this specific topic remains very limited; prospective trials with long-term follow-up are needed to improve our understanding on how these genomic tests fit when combined with our current clinical tools. As the literature matures, it is likely that newer risk calculators that combine our classic clinical variables with genomic and imaging data will be developed to bring about standard protocols for prostate cancer decision-making.

Transparency of racial participation reporting in randomized controlled trials of minimally invasive surgical techniques.

BACKGROUND: Enrolment of racial/ethnic minorities in randomized controlled trials (RCTs) has historically been poor, despite efforts at improving access to RCTs. Under-representation of racial/ethnic minorities limits the external validity and generalizability of trials. Our objective was to determine to what extent are published RCTs of minimally invasive surgical techniques reporting the racial composition of their study cohorts and to describe the racial composition of patients enrolled in these trials, where data were available. METHODS: EMBASE (OvidSP®), MEDLINE (OvidSP®), and Cochrane (Wiley®) databases were systematically searched from inception to December 22, 2017 to identify all RCTs comparing minimally invasive and classical surgical techniques. The Mann-Kendall trend test was used to evaluate reporting trends over the study period. Predictors of racial reporting were evaluated using logistic regression analyses. RESULTS: Our search strategy yielded 9,321 references of which 496 RCTs met our inclusion/exclusion criteria. Racial information was reported in 20 (4.03%) studies. There was no significant improvement in racial reporting over the study period (p for trend = 0.31). Of the 17 different patient populations accounting for the 20 RCTs, 14 (82.4%) originated from the USA. Multicenter RCTs had significantly increased likelihood of reporting racial composition of the patient cohort (odds ratio 5.10, p = 0.025). White/Caucasian patients accounted for 84.5% of the pooled patient population, with Black/African American, Asian and Latin/Hispanic patients accounting for 7.9%, 1.2%, and 2.1%, respectively. CONCLUSIONS: Among RCTs assessing minimally invasive surgical techniques over the past 30 years, data on included patients' race is poorly reported. In addition to important efforts to improve access to clinical trials for racial and ethnic minorities, efforts aimed at improving reporting and transparency of surgical RCTs are sorely needed.

The effect of tetrahydrocannabinol on testosterone among men in the United States: results from the National Health and Nutrition Examination Survey.

PURPOSE: To determine the association between tetrahydrocannabinol (THC) use and testosterone (T) levels among men in the United States. METHODS: Using the National Health and Nutrition Examination Survey (NHANES) data from the years 2011-2016, we identified all men 18 years and older who answered the substance use questionnaire and underwent laboratory testing for T. Regular THC users were defined as those who use THC at least one time per month, every month for at least 1 year. Multivariable linear regressions controlling for confounders were then used to determine the relationship between THC use and T levels. RESULTS: Among the 5146 men who met inclusion, 3027 endorsed using THC at least once in their life (ever-user). Nearly half of the THC ever-users (49.3%) were considered regular THC users. Multivariate analysis controlling for age, comorbidities, tobacco use, alcohol use, body mass index (BMI), exercise level, and race revealed a small but statistically significant increase in T among regular THC users at any measured level of use, compared to non-regular THC users (non-users). This increase was characterized by an inverse U-shaped trend with Regular THC users using two-three times per month demonstrating the greatest increase in T (+ 66.77 ng/dL) over non-users. CONCLUSION: THC use is associated with small increases in testosterone. This increase in T appears to decline as THC use increases, but nevertheless, T is still higher with any amount of regular use when compared to T in non-users. Prospective work is needed to validate the observed increase and to better elucidate the mechanism of impact THC use has on T levels.

A Systematic Review of Reported Ejaculatory Dysfunction in Clinical Trials Evaluating Minimally Invasive Treatment Modalities for BPH.

PURPOSE OF REVIEW: To explore the sexual outcomes following the novel minimally invasive surgical procedures for benign prostatic hyperplasia- (BPH-) related lower urinary tract symptoms (LUTS), with an emphasis on ejaculatory dysfunction (EjD). RECENT FINDINGS: A database search with a 10-year time restriction was carried out until February 20, 2020 using MEDLINE through the PubMed Platform evaluating minimally invasive treatment modalities for BPH and their effect on EjD. After the article selection, we retrieved data for men randomized in 19 different studies with results in 40 separate published articles investigating minimally invasive BPH surgery and reporting EjD rates. To date, water vapor thermal therapy or Rezum, prostatic urethral lift (PUL) or UroLift®, prostate artery embolization (PAE), and Aquablation showed acceptable rates (< 2%) of retrograde ejaculation by 1 year and had very low adverse events related to the procedure. Both PUL and Rezum demonstrated lower rates when compared with PAE and Aquablation. With comparable sexual side effect profiles postoperatively, clinicians may determine which therapeutic modality is optimal for patients based on efficacy and cost-benefit. Further randomized clinical trials are required to directly compare the effect of novel minimally invasive surgical procedures for BPH-related LUTS on ejaculation and sexual function.

A Surgeon's Guide to the Various Antibiotic Dips Available During Penile Prosthesis Implantation.

PURPOSE OF REVIEW: Inflatable penile prosthesis (IPP) is a treatment for erectile dysfunction. IPPs have undergone improvements; however, post-surgical infections still occur. Furthermore, the type of pathogens infecting the implants has changed recently from Gram-positive to Gram-negative bacteria and fungi due to advances in antibiotic dips targeting the skin flora. To protect against infection, the AMS 700 is pre-coated with InhibiZone (mixture of Rifampin/Minocycline) and the Coloplast Titan, with several antibiotic dip options of differing efficacies. This review discusses strategies to decrease the infection rates in implant surgery, focusing on antibiotic dips. RECENT FINDINGS: Current research endorses the use of rifampin/gentamicin as the most studied combination; however, some studies have utilized different dips for additional coverage including the InhibiZone on the AMS 700. With the increasing prevalence of diabetes and Gram-negative organisms, there is a need to develop strategies for increased coverage against infections. Controlled studies with different antibiotic combinations are needed to identify the ideal cocktail to decrease infection.

Artificial Intelligence in Reproductive Urology.

PURPOSE OF REVIEW: The promise of artificial intelligence (AI) in medicine has been widely theorized over the past couple of decades. It has only been with technological advances over the past few years that physicians and computer scientists have started discovering its true clinical potential. Reproductive urology is a sub-discipline that AI could be of great contribution, as current predictive models and subjectivity within the field have several limitations. We review the literature to summarize recent AI applications in reproductive urology. RECENT FINDINGS: Early AI applications in reproductive urology focused on predicting semen parameters based on questionnaires that identify potential environmental factors and/or lifestyle habits impacting male fertility. AI has shown success in predicting the patient subpopulation most likely to need a genetic workup for azoospermia. With recent advances in image processing, automated sperm detection is a reality. Semen analyses, once a laboratory-only diagnostic test, have moved into health consumer homes with the advent of AI. AI's prospects in medicine are considerable and there is strong potential for AI within reproductive urology. Research in identifying the factors that can affect reproductive success either naturally or with assisted reproduction is of paramount importance to move the field forward.

Hyaluronic acid family in bladder cancer: potential prognostic biomarkers and therapeutic targets.

BACKGROUND: Molecular markers of clinical outcome may aid in designing targeted treatments for bladder cancer. However, only a few bladder cancer biomarkers have been examined as therapeutic targets. METHODS: Data from The Cancer Genome Atlas (TCGA) and bladder specimens were evaluated to determine the biomarker potential of the hyaluronic acid (HA) family of molecules - HA synthases, HA receptors and hyaluronidase. The therapeutic efficacy of 4-methylumbelliferone (4MU), a HA synthesis inhibitor, was evaluated in vitro and in xenograft models. RESULTS: In clinical specimens and TCGA data sets, HA synthases and hyaluronidase-1 levels significantly predicted metastasis and poor survival. 4-Methylumbelliferone inhibited proliferation and motility/invasion and induced apoptosis in bladder cancer cells. Oral administration of 4MU both prevented and inhibited tumour growth, without dose-related toxicity. Effects of 4MU were mediated through the inhibition of CD44/RHAMM and phosphatidylinositol 3-kinase/AKT axis, and of epithelial-mesenchymal transition determinants. These were attenuated by HA, suggesting that 4MU targets oncogenic HA signalling. In tumour specimens and the TCGA data set, HA family expression correlated positively with ß-catenin, Twist and Snail expression, but negatively with E-cadherin expression. CONCLUSIONS: This study demonstrates that the HA family can be exploited for developing a biomarker-driven, targeted treatment for bladder cancer, and 4MU, a non-toxic oral HA synthesis inhibitor, is one such candidate.

Impact of 2004 ISUP/WHO classification on bladder cancer grading.

PURPOSE: To determine whether implementation of the 2004 WHO/ISUP bladder cancer (BCa) grading system caused a grade migration, i.e., more tumors being graded as high grade (HG). METHODS: Data on 1040 BCa cases from 668 patients treated at our institution between 2000 and 2013 and reviewed by six pathologists were evaluated: low grade (LG): 249; HG: 791; Ta: 389; T1: 214; CIS: 95; ≥T2: 342. Differences in LG or HG cases (expressed as %BCa cases/year) were analyzed by Mann-Whitney test. Correlation between the year of diagnosis and clinical/pathological parameters was evaluated by logistic regression analyses. RESULTS: During the study period, BCa cases diagnosed as LG significantly decreased with a corresponding increase in HG cases. Nonlinear regression analysis indicated that ~2008 was the crossover point for grade migration; %LG: 31.8 ± 4.8 (2000-2007); 14.1 ± 7.0 (2008-2013); %HG: 68.2 ± 4.8 (2000-2007); 85.9 ± 6.9 (2008-2013), P = 0.004. The grade migration was confined to Ta cases with %LG Ta cases diagnosed decreasing by 3.6-fold from 2000-2007 to 2008-2013 (P = 0.004). Univariate and multivariate analyses confirmed the grade migration following the adoption of the 2004 system (P < 0.0001). Kaplan-Meier curves showed no significant differences between the two time intervals in terms of disease progression (P > 0.05). CONCLUSIONS: Implementation of the 2004 WHO/ISUP system caused a significant increase in pathologists grading Ta cases as HG; however, this increase did not seem to correlate with disease progression. Since LG and HG Ta tumors are treated differently, grade migration may impact the clinical management of BCa patients.

Differential expression of SDF-1 isoforms in bladder cancer.

PURPOSE: SDF-1 is a ligand of the chemokine receptors CXCR4 and 7. The 6 known SDF-1 isoforms are generated by alternative mRNA splicing. While SDF-1 expression has been detected in various malignancies, only few groups have reported differential expression of SDF-1 isoforms and its clinical significance. We evaluated the expression of 3 SDF-1 isoforms (α, ß and γ) in bladder cancer. MATERIALS AND METHODS: Using quantitative polymerase chain reaction we measured SDF-1α, ß and γ mRNA levels in 25 normal and 44 bladder cancer tissues, and in 210 urine specimens (28 normal, 74 benign, 57 bladder cancer, 35 bladder cancer history, 8 other cancer history and 8 other cancer) from consecutive patients. Levels were correlated with clinical outcome. RESULTS: Of the SDF-1 isoforms only SDF-1ß mRNA was significantly over expressed 2.5-fold to sixfold in bladder cancer compared to normal bladder tissues. SDF-1α was expressed in bladder tissues but SDF-1γ was undetectable. On multivariate analysis SDF-1ß was an independent predictor of metastasis and disease specific mortality (p=0.017 and 0.043, respectively). In exfoliated urothelial cells only SDF-1ß mRNA levels were differentially expressed with 91.2% sensitivity and 73.8% specificity for detecting bladder cancer. In patients with a bladder cancer history increased SDF-1ß levels indicated a 4.3-fold increased risk of recurrence within 6 months (p=0.0001). CONCLUSIONS: SDF-1 isoforms are differentially expressed in bladder tissues and exfoliated urothelial cells. SDF-1ß mRNA levels in bladder cancer tissues predict a poor prognosis. Furthermore, SDF-1ß mRNA levels in exfoliated cells detect bladder cancer with high sensitivity and they are a potential predictor of future recurrence.

Classification and Risk Factors for Surgical Site Infections in Radical Cystectomy: A 16-Year Analysis.

Introduction: Surgical site infection (SSI) is a substantial cause of peri-operative morbidity among patients undergoing radical cystectomy (RC). The purpose of this study was to identify the risk factors of SSI after RC and to classify and characterize treatment of SSIs. Methods: We retrospectively analyzed peri-operative characteristics and SSI, for patients undergoing RC from 2007 to 2022. Patients were stratified by SSI versus no SSI and differences were assessed. Uni-variable/multi-variable logistic regression analyses were performed to identify factors associated with SSI. SSIs were categorized by the Centers for Disease Control and Prevention (CDC) type: Superficial incisional, deep incisional, and organ/space confined. Results: Three hundred and ninety-eight patients had RC, 279 open, and 119 robotic; 78 (19.6%) developed SSI. Cohorts were similar demographically. Length of stay (LOS) was longer in the SSI cohort (8.8 d versus 12.4 d, p < 0.001), and body mass index (BMI) was greater in patients with SSI (24.34 vs. 25.39, p = 0.0003). On uni-variable analysis, age, gender, Charlson Comorbidity Index, diabetes mellitus, diversion, odds ratio (OR) time, blood loss, and open versus robotic technique were not substantial SSI predictors. BMI was an independent risk factor for SSI on both uni-variable (OR: 1.07, 95% confidence interval [CI]: 1.018-1.115, p = 0.0061) and multi-variable analysis (OR: 1.06, 95% CI: 1.009-1.109, p = 0.02) for 10 (12.8%) and 24 (30.8%) superficial and deep-incisional SSIs, respectively. Superficial wound SSI was treated conservatively with 60% receiving antibiotic agents and no procedural intervention. Deep SSIs received antibiotic agents and 50% required surgical intervention. There were 44 (56.4%) organ/space SSIs, and the most common treatment was antibiotic agents (100%) and IR drain placement (30, 68.2%). Conclusion: In patients undergoing RC, BMI was an independent risk factor for SSI. Type of the surgical procedure, robotic versus open, was not predictive of SSI. LOS was longer for patients with SSI. SSI was managed differently depending on CDC classification.

C-X-C chemokine receptor 7: a functionally associated molecular marker for bladder cancer.

BACKGROUND: C-X-C chemokine receptor 4 (CXCR4) and CXCR7 are 7-transmembrane chemokine receptors of the stroma-derived factor (SDF-1). CXCR4, but not CXCR7, has been examined in bladder cancer (BCa). This study examined the functional and clinical significance of CXCR7 in BCa. METHODS: CXCR4 and CXCR7 levels were measured in BCa cell lines, tissues (normal = 25; BCa = 44), and urine specimens (n = 186) by quantitative polymerase chain reaction and/or immunohistochemistry. CXCR7 function in BCa cells were examined by transient transfections using a CXCR7 expression vector or small interfering RNA. RESULTS: In BCa cell lines, CXCR7 messenger RNA levels were 5- to 37-fold higher than those for CXCR4. Transient overexpression of CXCR7 in BCa cell lines promoted growth and chemotactic motility. CXCR7 colocalized and formed a functional complex with epidermal growth factor receptor, phosphoinositide 3-kinase/Akt, Erk, and src and induced their phosphorylation. CXCR7 also induced up-regulation of cyclin-D1 and bcl-2. Suppression of CXCR7 expression reversed these effects and induced apoptosis. CXCR7 messenger RNA levels and CXCR7 staining scores were significantly (5- to 10-fold) higher in BCa tissues than in normal tissues (P < .001). CXCR7 expression independently associated with metastasis (P = .019) and disease-specific mortality (P = .03). CXCR7 was highly expressed in endothelial cells in high-grade BCa tissues when compared to low-grade BCa and normal bladder. CXCR7 levels were elevated in exfoliated urothelial cells from high-grade BCa patients (P = .0001; 90% sensitivity; 75% specificity); CXCR4 levels were unaltered. CONCLUSIONS: CXCR7 promotes BCa cell proliferation and motility plausibly through epidermal growth factor receptor receptor and Akt signaling. CXCR7 expression is elevated in BCa tissues and exfoliated cells and is associated with high-grade and metastasis.

Prognostic implications of partial sampling of radical prostatectomy specimens: comparison of 3 methods.

PURPOSE: We analyzed the prognostic implications of positive margins and extraprostatic extension missed by different methods of partially sampling prostatectomy specimens. MATERIALS AND METHODS: The study group consisted of 1,499 patients treated with radical prostatectomy. All specimens were processed uniformly and submitted entirely. For each patient with a positive margin or extraprostatic extension we determined whether these pathological characteristics would have been diagnosed had the specimen been examined by 3 partial sampling techniques. The Harrell concordance index was used to quantify the predictive performance of the Cox models based on the potential findings of the different sampling methods. RESULTS: Partial sampling methods 1 and 2, which included the examination of alternate slides, missed 13% to 21% of positive margins and 27% to 46% of extraprostatic extensions. The effect on biochemical recurrence-free survival of these undetected pathological features was similar to that of positive margins and extraprostatic extension that would have been diagnosed by corresponding techniques. Method 3, which sampled the entire posterior region, the mid anterior prostate and the rest of the ipsilateral anterior gland (if sizeable tumor was seen), detected 95% of positive margins and 94% of extraprostatic extensions. The extraprostatic extension missed by this method was not associated with a significant increase in the risk of biochemical recurrence. The Harrell concordance index of the multivariate models was 0.806, 0.797, 0.795 and 0.804 based on the results of complete sampling, and methods 1, 2 and 3, respectively. CONCLUSIONS: Examining alternate sections of prostatectomy specimen results in missing clinically important positive margins and extraprostatic extension. It decreases our ability to predict biochemical recurrence-free survival.

Comprehensive analysis of post-diagnostic prostate-specific antigen kinetics as predictor of a prostate cancer progression in active surveillance patients.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: A significant proportion of patients diagnosed with prostate cancer do not require immediate treatment and could be managed by active surveillance, which usually includes serial measurements of prostate-specific antigen (PSA) levels and regular biopsies. The rate of rise in PSA levels, which could be calculated as PSA velocity or PSA doubling time, was previously suggested to be associated with the biological aggressiveness of prostate cancer. Although these parameters are obvious candidates for predicting tumour progression in active surveillance patients, earlier studies that examined this topic provided conflicting results. Our analysis showed that PSA velocity and PSA doubling time calculated at different time-points, by different methods, over different intervals, and in different sub-groups of active surveillance patients provide little if any prognostic information. Although we found some significant associations between PSA velocity and the risk of progression as determined by biopsy, the actual clinical significance of this association was small. Furthermore, PSA velocity did not add to the predictive accuracy of total PSA. OBJECTIVE: To study whether prostate-specific antigen (PSA) velocity (PSAV) and PSA doubling time (PSADT) are associated with biopsy progression in patients managed by active surveillance. PATIENTS AND METHODS: Our inclusion criteria for active surveillance are biopsy Gleason sum <7, two or fewer positive biopsy cores, ≤20% tumour present in any core, and clinical stage T1-T2a. Changes in any of these parameters during the follow-up that went beyond these limits are considered to be progression. This study included 250 patients who had at least one surveillance biopsy, an available PSA measured no earlier than 3 months before diagnosis, and at least one PSA measurement before each surveillance biopsy. We evaluated the association between PSA kinetics and progression at successive surveillance biopsies in different sub-groups of patients by calculating the area under the curve (AUC) as well as sensitivity and specificity of different thresholds. RESULTS: Over a median follow-up of 3.0 years, the disease of 64 (26%) patients progressed. PSADT was not associated with biopsy progression, whereas PSAV was only weakly associated with progression in certain sub-groups. However, incorporation of PSAV in models including total PSA resulted in a moderate increase in AUC only when the entire cohort was analysed. In other sub-groups the predictive accuracy of total PSA was not significantly improved by adding PSAV. CONCLUSIONS: Our findings confirm that PSA kinetics should not be used in decision-making in patients with low-risk prostate cancer managed by active surveillance. Regular surveillance biopsies should remain as the principal method of monitoring cancer progression in these men.

Galectin-3 expression in prostate cancer and benign prostate tissues: correlation with biochemical recurrence.

BACKGROUND: Galactin-3 is a cell adhesion molecule involved in tumor progression. Our aim was to examine Gal-3 expression in tumor, benign tissue adjacent to the tumor (adjacent-benign) and benign prostate specimens and correlated it with biochemical recurrence. MATERIALS AND METHODS: Tissue microarrays were prepared from 83 tumor, 78 adjacent-benign and 75 benign tissues obtained from 83 patients undergoing prostatectomy for clinically localized prostate cancer. Tissues were stained using a Gal-3 antibody and immunohistochemistry. The staining was graded between 0 and 300 depending upon staining intensity and the area of staining. In 37 patients on whom there was follow-up (Mean: 57.8 months; Median: 68 months), staining intensity was correlated with biochemical recurrence. RESULTS: Gal-3 showed both nuclear and cytoplasmic localization in benign, adjacent-benign and tumor tissues. Median Gal-3 staining scores significantly decreased from benign (192.5) to adjacent-benign (148.8 p = 0.007) and to tumor (108.8; p < 0.0001) tissues. In univariate analysis, age (p = 0.028), Gleason sum (p = 0.007), T stage (p = 0.011), seminal vesicle invasion (p = 0.009), pre-operative prostate-specific antigen (p = 0.045) and Gal-3 staining in tumor tissues (0.018) significantly correlated with biochemical recurrence. In multivariate analysis, Gal-3 expression in tumor (p = 0.04), adjacent-benign (p = 0.037) and benign (p = 0.005) tissues significantly correlated with biochemical recurrence. Gal-3 staining in tumor tissues had 91.7 % sensitivity, 64 % specificity and 73 % accuracy in predicting biochemical recurrence. CONCLUSIONS: This is the first study that showed a decreasing gradient of Gal-3 expression in benign, adjacent-benign and tumor tissues. Gal-3 expression may be useful in predicting biochemical recurrence.

Low-intensity extracorporeal shockwave therapy for diabetic men with erectile dysfunction: A systematic scoping review.

BACKGROUND: Erectile dysfunction (ED) is a very common complication in men with diabetes mellitus (DM). Low-intensity extracorporeal shockwave therapy (Li-ESWT) offers a promising nonsurgical treatment option for ED. A systematic scoping review investigating the outcomes of Li-ESWT in diabetic men with ED has not yet been performed. OBJECTIVES: To systematically review animal and clinical studies related to the use of Li-ESWT for treatment of DM-related ED. DATA SOURCES: PubMed, Embase, The Cochrane Library, Scopus, and Web of Science were searched, unrestricted by dates or study design. MATERIALS AND METHODS: We included qualitative studies, quantitative studies, primary research studies, meta-analyses, and research letters written in English. Full text reviewing was completed in all animal and human studies discussing Li-ESWT for the treatment of ED in subjects with DM. Data extracted included the journal citation, publication year, country of origin, study design, and a summary of the pertinent findings. RESULTS: Our search yielded nine clinical studies and 10 animal studies. The results of the clinical studies suggest that Li-ESWT is a safe and effective treatment in men with well-controlled DM and moderate or better ED. However, the benefit is less durable in diabetic men than nondiabetic men. The results of the animal studies suggest that Li-ESWT can significantly improve erectile function in diabetic rat models with ED. CONCLUSIONS: The examined studies present encouraging results for the use of Li-ESWT to treat diabetic men with ED. Future studies, particularly robust randomized controlled trials, are necessary to confirm these findings and provide long-term follow-up.